Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Given the growing evidence of gut microbiota being involved in psychiatric (including neurodevelopmental) disorders, we aimed to identify differences in gut microbiota composition between participants with ADHD and controls and to investigate the role of the microbiota in inattention and hyperactivity/impulsivity. Fecal samples were collected from 107 participants (N_ADHD = 42; N_controls = 50; N_{subthreholdADHD} = 15; range age: 13–29 years). The relative quantification of bacterial taxa was done using 16S ribosomal RNA gene amplicon sequencing. Alpha and Beta-diversity were not different between participants with ADHD and healthy controls. Three genera showed nominal differences (p_uncorrected < 0.05) between both groups (Prevotella_9, Coprococcus_2 and Intestinibacter) and were further tested for their association with ADHD symptom scores (adjusting for age, sex, body mass index, a time delay between feces collection and symptoms assessment, medication use and family relatedness). Our results show that the variation of a genus from the Lachnospiraceae family (Coprococcus_2) showed a trend of being negatively associated with inattention symptoms. Furthermore, we showed that the relative abundance of four genera was reduced by ADHD medication (p_uncorrected < 0.05). Overall, our results may support the role of the gut microbiota in the pathophysiology of ADHD. Given the scarcity of studies on the gut microbiota in individuals with ADHD, the current results are an important contribution to this field. More studies are needed into the gut microbiota as part of the pathology of ADHD, especially with a bigger sample size across the lifespan and more detailed information about lifestyle.

Background: Compared to typically developing individuals, individuals with attention-deficit-hyperactivity disorder (ADHD) are on average more often exposed to stressful conditions (e.g., school failure, family conflicts, financial problems). We hypothesized that high exposure to stress relates to a more persistent and complex (i.e., multi-problem) form of ADHD, while low-stress exposure relates to remitting ADHD over the course of adolescence. Method: Longitudinal data (ages 11, 13, 16, and 19) came from the Tracking Adolescents’ Individual Life Survey (TRAILS). We selected children diagnosed with ADHD (n = 244; 167 males; 77 females) from the TRAILS clinical cohort and children who screened positive (n = 365; 250 males; 115 females) and negative (gender-matched: n = 1222; 831 males; 391 females) for ADHD from the TRAILS general population sample cohort (total n = 1587). Multivariate latent class growth analysis was applied to parent- and self-ratings of stress exposure, core ADHD problems (attention problems, hyperactivity/impulsivity), effortful control, emotion dysregulation (irritability, extreme reactivity, frustration), and internalizing problems (depression, anxiety, somatic complaints). Results: Seven distinct developmental courses in stress exposure and psychopathology were discerned, of which four related to ADHD. Two persistent ADHD courses of severely affected adolescents were associated with very high curvilinear stress exposure peaking in mid-adolescence: (1) Severe combined type with ongoing, severe emotional dysregulation, and (2) combined type with a high and increasing internalization of problems and elevated irritability; two partly remitting ADHD courses had low and declining stress exposure: (3) inattentive type, and (4) moderate combined type, both mostly without comorbid problems. Conclusions: High-stress exposure between childhood and young adulthood is strongly intertwined with a persistent course of ADHD and with comorbid problems taking the form of either severe and persistent emotion dysregulation (irritability, extreme reactivity, frustration) or elevated and increasing irritability, anxiety, and depression. Conversely, low and declining stress exposure is associated with remitting ADHD and decreasing internalizing and externalizing problems. Stress exposure is likely to be a facilitating and sustaining factor in these two persistent trajectories of ADHD with comorbid problems into young adulthood. Our findings suggest that a bidirectional, continuing, cycle of stressors leads to enhanced symptoms, in turn leading to more stressors, and so forth. Consideration of stressful conditions should, therefore, be an inherent part of the diagnosis and treatment of ADHD, to potentiate prevention and interruption of adverse trajectories.

Attention-deficit/hyperactivity disorder (ADHD) is associated with substance use disorders (SUD; alcohol and/or drug dependence) and nicotine dependence. This study aims to advance our knowledge about the association between SUD, nicotine dependence, and the course of ADHD (persistent versus remittent ADHD and late-onset ADHD). ADHD, SUD, and nicotine dependence were longitudinally assessed (mean age at study entry 11.3 years, mean age at follow-up 21.1 years) using structured psychiatric interviews and multi-informant questionnaires in a subsample of the Dutch part of the International Multicenter ADHD Genetics study. Individuals with persistent ADHD (n = 62), remittent ADHD (n = 12), late-onset ADHD (n = 18; age of onset after 12 years), unaffected siblings (n = 50), and healthy controls (n = 47) were assessed. Hazard ratios (HR) with 95% confidence intervals (CIs) were estimated by Cox regression and adjusted for clustered family data, gender, follow-up length, and current age. Individuals with persistent ADHD were at significantly higher risk of development of SUD relative to healthy controls (HR = 4.56, CI 1.17–17.81). In contrast, levels of SUD in those with remittent ADHD were not different from healthy controls (HR = 1.00, CI .07–13.02). ADHD persisters had also higher prevalence rates of nicotine dependence (24.2%) than ADHD remitters (16.7%) and healthy controls (4.3%). A similar pattern was found in initially unaffected siblings who met ADHD criteria at follow-up (“late-onset” ADHD); they had also a higher prevalence of SUD (33%) compared to stable unaffected siblings (20%) and were at significantly increased risk of development of nicotine dependence compared to healthy controls (HR = 13.04, CI 2.08–81.83). SUD and nicotine dependence are associated with a negative ADHD outcome. Results further emphasize the need for clinicians to comprehensively assess substance use when diagnosing ADHD in adolescents and adults.

Motor coordination problems are frequent in children with attention deficit/hyperactivity disorder (ADHD). We performed a genome-wide association study to identify genes contributing to motor coordination problems, hypothesizing that the presence of such problems in children with ADHD may identify a sample of reduced genetic heterogeneity.; Children with ADHD from the International Multicentre ADHD Genetic (IMAGE) study were evaluated with the Parental Account of Children's Symptoms. Genetic association testing was performed in PLINK on 890 probands with genome-wide genotyping data. Bioinformatics enrichment-analysis was performed on highly ranked findings. Further characterization of the findings was conducted in 313 Dutch IMAGE children using the Developmental Coordination Disorder Questionnaire (DCD-Q).; Although none of the findings reached genome-wide significance, bioinformatics analysis of the top-ranked findings revealed enrichment of genes for motor neuropathy and amyotrophic lateral sclerosis. Genes involved in neurite outgrowth and muscle function were also enriched. Among the highest ranked genes were MAP2K5, involved in restless legs syndrome, and CHD6, causing motor coordination problems in mice. Further characterization of these findings using DCD-Q subscales found nominal association for 15 SNPs.; Our findings provide clues about the aetiology of motor coordination problems, but replication studies in independent samples are necessary

Autism spectrum disorder (ASD) traits are continuously distributed throughout the population, and ASD symptoms are also frequently observed in patients with attention-deficit/hyperactivity disorder (ADHD). Both ASD and ADHD have been linked to alterations in reward-related neural processing. However, whether both symptom domains interact and/or have distinct effects on reward processing in healthy and ADHD populations is currently unknown. We examined how variance in ASD and ADHD symptoms in individuals with ADHD and healthy participants was related to the behavioural and neural response to reward during a monetary incentive delay (MID) task. Participants (mean age: 17.7 years, range: 10–28 years) from the NeuroIMAGE study with a confirmed diagnosis of ADHD (n = 136), their unaffected siblings (n = 83), as well as healthy controls (n = 105) performed an MID task in a magnetic resonance imaging (MRI) scanner. ASD and ADHD symptom scores were used as predictors of the neural response to reward anticipation and reward receipt. Behavioural responses were modeled using linear mixed models; neural responses were analysed using FMRIB’s Software Library (FSL) proprietary mixed effects analysis (FLAMEO). ASD and ADHD symptoms were associated with alterations in BOLD activity during reward anticipation, but not reward receipt. Specifically, ASD scores were related to increased insular activity during reward anticipation across the sample. No interaction was found between this effect and the presence of ADHD, suggesting that ASD symptoms had no differential effect in ADHD and healthy populations. ADHD symptom scores were associated with reduced dorsolateral prefrontal activity during reward anticipation. No interactions were found between the effects of ASD and ADHD symptoms on reward processing. Variance in ASD and ADHD symptoms separately influence neural processing during reward anticipation in both individuals with (an increased risk of) ADHD and healthy participants. Our findings therefore suggest that both symptom domains affect reward processing through distinct mechanisms, underscoring the importance of multidimensional and multimodal assessment in psychiatry.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are frequently comorbid disorders. Emotion recognition problems are considered an important familial deficit in ASD, but this is unknown in ADHD. Very few studies have directly compared emotion recognition performance of youth with ASD and/or ADHD and of their unaffected siblings across age to quantify the contribution of emotion recognition problems to the ADHD phenotype. We therefore devised a study of 64 ASD+ADHD participants, 89 ASD-only participants, 111 ADHD-only participants, 122 unaffected ASD(+ADHD) siblings, 69 unaffected ADHD-only siblings and 220 controls aged 7-18 years, who had completed two tasks assessing auditory and visual emotion recognition. Factor analysis was used to detect underlying dimensions of emotion recognition capacity. Linear mixed models were used to compare performance across groups and to assess age effects. The factor-analysis revealed four factors separating speed and accuracy regarding visual and auditory emotion recognition. ASD+ADHD, ASD-only, and ADHD-only participants all performed worse than controls. ASD+ADHD, ASD-only, and ADHD-only participants did not differ in the severity of their emotion recognition problems. Both unaffected sibling groups performed intermediate between patients and controls. For ASD+ADHD and ADHD-only participants, group differences were more marked in adolescence than childhood, whereas in ASD participants this was not observed. We conclude that emotion recognition problems are a familial deficit in ADHD to a similar extent as in ASD. Emotion recognition problems specifically - and social cognition problems more generally - should be assessed in clinical practice for ADHD.